FDA Sends CRL for COPD Triple-Combination Therapy PT010


The investigative ICS/LAMA/LABA inhaler therapy reported positive findings from its phase 3 ETHOS trial in August, though the results were not included in the FDA application.


The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) to AstraZeneca for its proposed triple-combination inhaler therapy for chronic obstructive pulmonary disease (COPD).

The investigative budesonide/glycopyrronium/formoterol fumarate (PT010) therapy’s application was supported by evidence from the phase 3 KRONOS trial, which compared the drug to dual glycopyrronium/formoterol fumarate (GFF; Bevespi Aerosphere) or budesonide/formoterol fumarate (PT009) in patients with moderate to very severe COPD.

The trial showed PT010 met 8 or 9 set primary endpoints compared to the standard dual therapy options.

However, at the time of AstraZeneca’s application to the FDA, results from the late-stage ETHOS trial were not available. Those results, initially updated in late August, showed PT010 with standard 320 mcg-dose budesonide reduced the rate of moderate or severe exacerbations in patients with COPD at a statistically significant rate versus GFF or PT009 in patients with COPD.

Along with meeting its primary outcome, the therapy’s safety and tolerability were shown to be consistent with the known profiles of its dual therapy competitors.

The ongoing 52-week, 8572-patient, randomized trial, which will be presented at an upcoming medical meeting, may show physicians a first look at outcomes comparing an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting beta agonist (ICS/LAMA/LABA) triple therapy to dual ICS/LABA and LAMA/LABA therapies.

“This is also the first time we have seen the benefit of fixed-dose triple-combination therapy at 2 inhaled corticosteroid doses, which could transform treatment practice by allowing physicians to select the optimal dose for individual patients,” lead investigator Klaus F. Rabe, MD, PhD, said in a statement at the time.

AstraZeneca expressed intent to work with the FDA regarding next steps to the CRL on Tuesday, and will likely submit ETHOS trial results along with the next application.

PT010 is currently approved for the treatment of COPD symptoms in Japan as Breztri Aerosphere, and is awaiting regulatory decisions in both China and the European Union.

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